Abstract
Outer hair cells (OHCs) are a mammalian innovation for mechanically amplifying sound energy to overcome the viscous damping of the cochlear partition. Although the voltage-dependent OHC membrane motor, prestin, has been demonstrated to be essential for mammalian cochlear amplification, the molecular mechanism by which prestin converts electrical energy into mechanical displacement/force remains elusive. Identifying mutations that alter the motor function of prestin provides vital information for unraveling the energy transduction mechanism of prestin. We show that the V499G/Y501H mutation does not deprive prestin of its voltage-induced motor activity, but it does significantly impair the fast motor kinetics and voltage operating range. Furthermore, mutagenesis studies suggest that Val-499 is the primary site responsible for these changes. We also show that V499G/Y501H prestin forms heteromers with wild-type prestin and that the fast motor kinetics of wild-type prestin is not affected by heteromer formation with V499G/Y501H prestin. These results suggest that prestin subunits are individually functional within a given multimer.
Highlights
Prestin converts electrical energy into mechanical work
We show that 499-prestin is functional as a voltage-dependent motor, the kinetics is significantly slowed
It should be emphasized that the mechanical independence of prestin subunits needs to be discussed separately for motor kinetics and voltage-operating point (Vpk)
Summary
Results: The V499G/Y501H mutation significantly impairs fast motor kinetics of prestin. Significance: V499G/Y501H mutated prestin provides clues to the molecular mechanisms underlying somatic electromotility and cochlear amplification. The voltage-dependent OHC membrane motor, prestin, has been demonstrated to be essential for mammalian cochlear amplification, the molecular mechanism by which prestin converts electrical energy into mechanical displacement/force remains elusive. We show that V499G/Y501H prestin forms heteromers with wildtype prestin and that the fast motor kinetics of wild-type prestin is not affected by heteromer formation with V499G/Y501H prestin. These results suggest that prestin subunits are individually functional within a given multimer
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